This proposal is to request support for a Keystone Symposia meeting entitled G Protein-Coupled Receptors, organized by Brian K. Kobilka, Martin J. Lohse and The W. Schwartz, which will be held in Breckenridge, Colorado from April 7 - 12, 2010. G protein-coupled receptors (GPCRs) constitute the largest family of membrane proteins in the human genome. This family includes many potential therapeutic targets for a broad range of diseases including: cardiovascular, pulmonary, and behavioral and neurodegenerative disorders, inflammation, cancer, diabetes and obesity. Successful development of new drugs for GPCRs has been disappointing in spite of having access to all GPCR sequences in the genome, as well as physiologic insights from gene modification technology, larger more diverse compound libraries, and advances in high-throughput screening technologies. The goal of this meeting is to examine the challenges facing GPCR drug discovery, and to explore the application of structural biology, genomics and proteomics to GPCR target selection, and to lead identification and optimization. The meeting will cover a broad range of topics relevant to GPCR drug discovery efforts including the following: GPCR structure, subcellular localization of GPCRs in signaling compartments, GPCR-signaling protein complexes, in vivo physiology, and in silico screening. PUBLIC HEALTH RELEVANCE: G protein-coupled receptors (GPCRs) constitute the largest family of membrane proteins in the human genome. This family includes many potential therapeutic targets for a broad range of diseases including: cardiovascular disease, respiratory and renal disease, diabetes and obesity, HIV infection and cancer, and neuropsychiatric disorders such as schizophrenia, depression and attention deficit disorder. The goal of the Keystone Symposia meeting on G Protein-Coupled Receptors is to examine the challenges facing GPCR drug discovery;and to explore the application of structural biology, genomics and proteomics to GPCR target selection, lead identification and optimization.